Database Query Results : , , OXPHOS

OXPHOS, Oxidative phosphorylation: Click to Expand ⟱
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Oxidative phosphorylation (or phosphorylation) is the fourth and final step in cellular respiration.
Alterations in phosphorylation pathways result in serious outcomes in cancer. Many signalling pathways including Tyrosine kinase, MAP kinase, Cadherin-catenin complex, Cyclin-dependent kinase etc. are major players of the cell cycle and deregulation in their phosphorylation-dephosphorylation cascade has been shown to be manifested in the form of various types of cancers.
Many tumors exhibit a well-known metabolic shift known as the Warburg effect, where glycolysis is favored over OxPhos even in the presence of oxygen. However, this is not universal.
Many cancers, including certain subpopulations like cancer stem cells, still rely on OXPHOS for energy production, biosynthesis, and survival.

– In several cancers, especially during metastasis or in tumors with high metabolic plasticity, OxPhos can remain active or even be upregulated to meet energy demands.

In some cancers, high OxPhos activity correlates with aggressive features, resistance to standard therapies, and poor outcomes, particularly when tumor cells exploit mitochondrial metabolism for survival and metastasis.

– Conversely, low OxPhos activity can be associated with a reliance on glycolysis, which is also linked with rapid tumor growth and certain adverse prognostic features.

Inhibiting oxidative phosphorylation is not a universal strategy against all cancers. Targeting OXPHOS can potentially disrupt the metabolic flexibility of cancer cells, leading to their death or making them more susceptible to other treatments.
Since normal cells also rely on OXPHOS, inhibitors must be carefully targeted to avoid significant toxicity to healthy tissues.
Not all tumors are the same. Some may be more glycolytic, while others depend more on mitochondrial metabolism. Therefore, metabolic profiling of tumors is crucial before adopting this strategy. Inhibiting OXPHOS is being explored in combination with other treatments (such as chemo- or immunotherapies) to improve efficacy and overcome resistance.

In cancer cells, metabolic reprogramming is a hallmark where cells often rely on glycolysis (known as the Warburg effect); however, many cancer types also depend on OXPHOS for energy production and survival. Targeting OXPHOS(using inhibitor) to increase the production of reactive oxygen species (ROS) can selectively induce oxidative stress and cell death in cancer cells.

-One side effect of increased OXPHOS is the production of reactive oxygen species (ROS).
-Many cancer cells therefore simultaneously upregulate antioxidant systems to mitigate the damaging effects of elevated ROS.
-Increase in oxidative phosphorylation can inhibit cancer growth.
Scientific Papers found: Click to Expand⟱
1340- 3BP,    Safety and outcome of treatment of metastatic melanoma using 3-bromopyruvate: a concise literature review and case study
- Review, NA, NA
Glycolysis↓, inhibiting key glycolysis enzymes
HK2↓,
LDH↓,
OXPHOS↓, inhibits mitochondrial oxidative phosphorylation
angioG↓,
H2O2↑, induces hydrogen peroxide generation in cancer cells (oxidative stress effect)
eff↑, Concurrent use of a GSH depletor(paracetamol) with 3BP killed resistant melanoma cells

1341- 3BP,    The HK2 Dependent “Warburg Effect” and Mitochondrial Oxidative Phosphorylation in Cancer: Targets for Effective Therapy with 3-Bromopyruvate
- Review, NA, NA
Glycolysis↓, second-generation glycolysis inhibitor.
OXPHOS↓,
*toxicity↓, Normal cells remain unharmed
ROS↑, well known that this compound generates ROS
GSH↓,
eff↑, 3BP demonstrates synergistic activity with other compounds that reduce intracellular levels of GSH

5271- 3BP,    The anticancer agent 3-bromopyruvate: a simple but powerful molecule taken from the lab to the bedside
- Review, Var, NA
selectivity↑, 3-bromopyruvate (3BP), a simple alkylating chemical compound was presented to the scientific community as a potent anticancer agent, able to cause rapid toxicity to cancer cells without bystander effects on normal tissues.
selectivity↑, results obtained in cancer research with this small molecule have contradicted the just noted general fear. Indeed, a promising drug has been revealed with an effective mechanism of action and an outstanding selectivity towards cancer cells
ATP↓, once inside cancer cells 3BP can then inhibit both of their energy (ATP) producing systems, i.e., glycolysis, likely by inhibiting hexokinase-2 (hk-2) and mitochondrial oxidative phosphorylation
Glycolysis↓,
HK2↓,
mt-OXPHOS↓,
GAPDH↓, Different reports have shown that 3BP is able to inhibit GAPDH activity leading to the loss of the ATP-producing steps that occur downstream of this enzyme
mtDam↑, Mitochondria related cell death has also been reported following 3BP treatment.
GSH↓, Ehrke and co-workers have demonstrated that 3BP inhibits glycolysis and deplete the glutathione levels in primary rat astrocytes
ROS↑, Others have also observed an increase in ROS levels following 3BP treatment that induces endoplasmic reticulum stress
ER Stress↑,
TumAuto↑, Autophagy has been associated with 3BP activity in breast cancer cell lines (Zhang et al., 2014),
LC3‑Ⅱ/LC3‑Ⅰ↑, 3BP leads to aggressive autophagy involving a decrease in the ratio of LC3I/LC3II and the levels of p62 as well as dephosphorylation of Akt and p53.
p62↓,
Akt↓,
HDAC↓, 3BP’s, it has been reported to be involved in suppressing epigenetic events as it inhibits histone deacetylase (HDAC) isoforms 1 and 3 in MCF-7 breast cancer cells leading to apoptosis
TumCA↑, Proliferation inhibition by 3BP treatment has also been related with the induction of S-phase and G2/M- phase arrest (Liu et al. 2009)
Bcl-2↓, downregulation of the expression of Bcl-2, c-Myc and mutant p53, the upregulation of Bax, activation of caspase-3 and mitochondrial leakage of cytochrome c
cMyc↓,
Casp3↑,
Cyt‑c↑,
Mcl-1↓, mitochondria mediated apoptosis triggered by 3BP was found to be associated with the downregulation of Mcl-1 through the phosphoinositide-3-kinase/Akt pathway (Liu et al. 2014).
PARP↓, 3BP treatment decreases the levels of poly(ADP-ribose) polymerase (PARP) and cleaved PARP.
ChemoSen↑, it might be a good adjuvant for commonly used chemotherapy agents, or a replacement for such agents.

5281- 3BP,    A translational study “case report” on the small molecule “energy blocker” 3-bromopyruvate (3BP) as a potent anticancer agent: from bench side to bedside
- Case Report, Var, NA
Glycolysis↓, 3BP targets cancer cells’ energy metabolism, both its high glycolysis (“Warburg Effect”) and mitochondrial oxidative phosphorylation.
mt-OXPHOS↓,
ATP↓, This inhibits/ blocks total energy production leading to a depletion of energy reserves. Moreover, 3BP as an “Energy Blocker”, is very rapid in killing such cells.
selectivity↑, 3BP at its effective concentrations that kill cancer cells has little or no effect on normal cells.
toxicity↝, The results obtained hold promise for 3BP as a future cancer therapeutic without apparent cyto-toxicity when formulated properly.
OS↑, The patient (Fig. 5) was able to survive a much longer period than expected with an improved quality of life, which is clearly attributable to the treatment with 3BP.
QoL↑,

5272- 3BP,    The efficacy of the anticancer 3-bromopyruvate is potentiated by antimycin and menadione by unbalancing mitochondrial ROS production and disposal in U118 glioblastoma cells
- in-vitro, GBM, U87MG - in-vitro, Nor, HEK293
Glycolysis↓, We used the antiglycolytic 3-bromopyruvate (3BP) as a metabolic modifier to treat U118 glioblastoma cell
ROS↑, ROS generated in mitochondria were enhanced at 30 μM 3BP, possibly by unbalancing their generation and their disposal because of glutathione peroxidase inhibition.
GPx↓,
eff↓, Indeed, the scavenger of mitochondrial superoxide MitoTEMPO counteracted 3BP-induced cyt c release and weakened the potentiating effect of 3BP/
OXPHOS↓, (3BP) is a reactive non-specific drug that can act as a metabolic modifier by interfering with glycolysis and oxidative phosphorylation in cancer cells
HK2↓, The mitochondrial hexokinase-II is the main target since its activity is specifically blocked by the formation of a pyruvinyl adduct after reacting with 3BP at the surface of the outer mitochondrial membrane
ATP↓, In malignant tumour cell lines, 3BP inhibits ATPase activity, reduces ATP levels, and reverses chemoresistance by antagonizing drug efflux by acting on the ATP-binding cassette transporters (
ROS↑, Furthermore, 3BP increases the production of reactive oxygen species (ROS) (Ihrlund et al., 2008; Kim et al., 2008; Macchioni et al., 2011a), induces ER stress,
ER Stress↑,
BioAv↓, Unfortunately, prolonged treatment with the drug reduces ROS levels and confers resistance by inducing regulatory genes that act on antioxidant systems.
Cyt‑c↑, 3BP induces cytochrome c release without triggering an apoptotic cascade in U118 cells
eff↑, The ROS enhancers antimycin and menadione sensitize U118 cells to 3BP

5257- 3BP,    Tumor Energy Metabolism and Potential of 3-Bromopyruvate as an Inhibitor of Aerobic Glycolysis: Implications in Tumor Treatment
- Review, Var, NA
Glycolysis↓, In recent years, a small molecule alkylating agent, 3-bromopyruvate (3-BrPA), being an effective glycolytic inhibitor, has shown great potential as a promising antitumor drug.
mt-OXPHOS↓, Not only it targets glycolysis process, but also inhibits mitochondrial OXPHOS in tumor cells.
HK2↓, The direct inhibition of mitochondrial HK-II isolated from the rabbit liver implanted VX2 tumor via 3-BrPA was demonstrated by Ko et al. [17].
Cyt‑c↑, -BrPA treatment resulted in an increase of cytochrome c release [59,60], along with an elevated expression of active proapoptotic caspase-3 and a decrease of antiapoptotic Bcl-2 and Mcl-1 [59]
Casp3↓,
Bcl-2↓,
Mcl-1↓,
GAPDH↓, Additionally, GAPDH was found to be inhibited by 3-BrPA in several studies
LDH↓, Recent reports showed 3-BrPA had ability to inhibit post glycolysis targets and other metabolic pathways, such as LDH, PDH, TCA cycle, and glutaminolysis
PDH↓, 3-BrPA was proven to be an inhibitor of PDH [72,73,74],
TCA↓,
GlutaM↓, this inhibition of TCA cycle can lead to the impairment of glutaminolysis due to α-KG generated from glutamine is incorporated into the TCA cycle by IDH and αKD activities
GSH↓, Indeed, a remarkable decrease of reduced glutathione (GSH) level was observed after 3-BrPA treatment in both microorganisms and various tumor cells [53,61,65].
ATP↓, 3-BrPA successfully killed AS-30D hepatocellular carcinoma (HCC) cells via the inhibition of both ATP-producing glycolysis and mitochondrial respiration [17].
mitResp↓,
ROS↑, the increase of ROS and concomitant decrease of GSH were commonly found in 3-BrPA-mediated antitumor studies [53,59,61,64,65,76,77,86,89].
ChemoSen↑, When 3-BrPA was combined with cisplatin or oxaliplatin with non-toxic low-dose, 3-BrPA strikingly enhanced the antiproliferative effects of both platinum drugs in HCT116 cells and resistant p53-deficient HCT116 cells [89].
toxicity↝, Finally, two years after the first diagnosis, the patient died due to an overload of liver function rather than the tumor itself [118].

5266- 3BP,    3-bromopyruvate-based agent KAT-101
- Review, Var, NA
eff↑, Upon oral administration of 3-BP-based agent KAT-101, the 3-BP derivative, being structurally similar to lactic acid, specifically binds to and enters cancer cells through monocarboxylic acid transporters (MCTs)
Glycolysis↓, KAT-101 interferes with both glycolysis and mitochondrial oxidative phosphorylation (OxPhos), thereby depleting adenosine triphosphate (ATP) levels and thus limits energy supply needed by cancer cells to proliferate.
OXPHOS↓,
ATP↓,
TumCP↓,
Apoptosis↑, This induces cancer cell apoptosis and prevents cancer cell proliferation.
HK2↓, In addition, KAT-101 is able to release mitochondrial-bound hexokinase (HK) II (HK2)
MPT↑, increases the formation of mitochondrial permeability transition pores (MPTPs), which induces apoptosis.
LDH↓, KAT-101 also inhibits a variety of enzymes, including lactate dehydrogenase (LDH), pyruvate dehydrogenase (PDH) and pyruvate dehydrogenase kinase (PDHK).
PDH↓,

3453- 5-ALA,    The heme precursor 5-aminolevulinic acid disrupts the Warburg effect in tumor cells and induces caspase-dependent apoptosis
- in-vitro, Lung, A549
OXPHOS↑, A549 exposed to ALA exhibited enhanced oxidative phosphorylation, which was indicated by an increase in COX protein expression and oxygen consumption.
OCR↑,
Warburg↓, These data demonstrate that ALA inhibits the Warburg effect and induces cancer cell death.
ROS↑, ALA significantly increased O2-generation over 4 h
SOD2↑, ALA stimulates MnSOD, catalase and HO-1 protein expression.
Catalase↑,
HO-1↑,
Casp3↑, ALA induced an increase in the protein expression of activated (cleaved) caspase-3.
Apoptosis↑, these data demonstrate that ALA induced caspase- dependent apoptosis in A549 cells.

3447- ALA,    Redox Active α-Lipoic Acid Differentially Improves Mitochondrial Dysfunction in a Cellular Model of Alzheimer and Its Control Cells
- in-vitro, AD, SH-SY5Y
*ATP↑, Incubation with ALA showed a significant increase in ATP levels in both SH-SY5Y-APP695 and SH-SY5Y-MOCK cells.
*MMP↑, MMP levels were elevated in SH-SY5Y-MOCK cells, treatment with rotenone showed a reduction in MMP, which could be partly alleviated after incubation with ALA in SH-SY5Y-MOCK cells.
*ROS↓, ROS levels were significantly lower in both cell lines treated with ALA.
*GlucoseCon↑, benefits to diabetic neuropathy and impaired glucose uptake, and the regeneration of glutathione (GSH) and vitamins C and E
*GSH↑,
*neuroP↑, ALA seems to have a positive effect on neurodegenerative diseases such as AD
*cognitive↑, ALA improves cognitive performance and could be considered as a promising bioactive substance for AD by affecting multiple mechanisms such as:
*Ach↑, (1) impaired acetylcholine production;
*Inflam↓, (2) hydroxyl radical formation, ROS production, and neuroinflammation;
*Aβ↓, (3) impaired amyloid plaque formation;
OXPHOS↓, ALA has also been shown to restore the expression of OXPHOS complexes in HepG2 cells, ranging in a concentration between 0.5–2 mM

1355- Ash,    Withaferin A-Induced Apoptosis in Human Breast Cancer Cells Is Mediated by Reactive Oxygen Species
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7 - in-vitro, Nor, HMEC
eff↑, WA treatment caused ROS production in MDA-MB-231 and MCF-7 cells, but not in a normal human mammary epithelial cell line (HMEC). ****
mt-ROS↑, WA-induced apoptosis in human breast cancer cells is mediated by mitochondria-derived ROS
mitResp↓,
OXPHOS↓, WA exposure was accompanied by inhibition of oxidative phosphorylation and inhibition of complex III activity.
compIII↑,
BAX↑,
Bak↑,
other↓, Cu,Zn-Superoxide dismutase (Cu,Zn-SOD) overexpression confers protection against WA-induced ROS production and apoptosis
ATP∅, steady-state levels of ATP were unaffected by WA treatment in either cell line
*ROS∅, but not in a normal human mammary epithelial cell line (HMEC). WA treatment caused ROS production in breast cancer cells, HMEC were resistant to pro-oxidant effect of this agent.

1142- Ash,    Ashwagandha-Induced Programmed Cell Death in the Treatment of Breast Cancer
- Review, BC, MCF-7 - NA, BC, MDA-MB-231 - NA, Nor, HMEC
Apoptosis↑,
ROS↑, anti-cancer effect of WA was significantly attenuated in the presence of anti-oxidants,
DNAdam↑,
OXPHOS↓, WA inhibits oxidative phosphorylation (OXPHOS) in Complex III, accompanied by apoptotic release of DNA fragments associated with histones in the cytosol
*ROS∅, WA shows high selectivity, causing ROS production only in MDA-MB-231 and MCF-7 cells, but not in the normal human mammary epithelial cell line (HMEC)
Bcl-2↓,
XIAP↓,
survivin↓,
DR5↑,
IKKα↓,
NF-kB↓,
selectivity↑, Moreover, WA shows high selectivity, causing ROS production only in MDA-MB-231 and MCF-7 cells, but not in the normal human mammary epithelial cell line (HMEC)
*ROS∅, Moreover, WA shows high selectivity, causing ROS production only in MDA-MB-231 and MCF-7 cells, but not in the normal human mammary epithelial cell line (HMEC)
eff↓, the anti-cancer effect of WA was significantly attenuated in the presence of anti-oxidants, as it has been shown that ectopic expression of Cu and Zn-superoxide dismutase (SOD) significantly weakens its apoptotic properties
Paraptosis↑, WA promotes death in both MCF-7 and MDA-MB-231 cell lines through paraptosis through the action of ROS

3166- Ash,    Exploring the Multifaceted Therapeutic Potential of Withaferin A and Its Derivatives
- Review, Var, NA
*p‑PPARγ↓, preventing the phosphorylation of peroxisome proliferator-activated receptors (PPARγ)
*cardioP↑, cardioprotective activity by AMP-activated protein kinase (AMPK) activation and suppressing mitochondrial apoptosis.
*AMPK↑,
*BioAv↝, The oral bioavailability was found to be 32.4 ± 4.8% after 5 mg/kg intravenous and 10 mg/kg oral WA administration.
*Half-Life↝, The stability studies of WA in gastric fluid, liver microsomes, and intestinal microflora solution showed similar results in male rats and humans with a half-life of 5.6 min.
*Half-Life↝, WA reduced quickly, and 27.1% left within 1 h
*Dose↑, WA showed that formulation at dose 4800 mg having equivalent to 216 mg of WA, was tolerated well without showing any dose-limiting toxicity.
*chemoPv↑, Here, we discuss the chemo-preventive effects of WA on multiple organs.
IL6↓, attenuates IL-6 in inducible (MCF-7 and MDA-MB-231)
STAT3↓, WA displayed downregulation of STAT3 transcriptional activity
ROS↓, associated with reactive oxygen species (ROS) generation, resulted in apoptosis of cells. The WA treatment decreases the oxidative phosphorylation
OXPHOS↓,
PCNA↓, uppresses human breast cells’ proliferation by decreasing the proliferating cell nuclear antigen (PCNA) expression
LDH↓, WA treatment decreases the lactate dehydrogenase (LDH) expression, increases AMP protein kinase activation, and reduces adenosine triphosphate
AMPK↑,
TumCCA↑, (SKOV3 andCaOV3), WA arrest the G2/M phase cell cycle
NOTCH3↓, It downregulated the Notch-3/Akt/Bcl-2 signaling mediated cell survival, thereby causing caspase-3 stimulation, which induces apoptosis.
Akt↓,
Bcl-2↓,
Casp3↑,
Apoptosis↑,
eff↑, Withaferin-A, combined with doxorubicin, and cisplatin at suboptimal dose generates ROS and causes cell death
NF-kB↓, reduces the cytosolic and nuclear levels of NF-κB-related phospho-p65 cytokines in xenografted tumors
CSCs↓, WA can be used as a pharmaceutical agent that effectively kills cancer stem cells (CSCs).
HSP90↓, WA inhibit Hsp90 chaperone activity, disrupting Hsp90 client proteins, thus showing antiproliferative effects
PI3K↓, WA inhibited PI3K/AKT pathway.
FOXO3↑, Par-4 and FOXO3A proapoptotic proteins were increased in Pten-KO mice supplemented with WA.
β-catenin/ZEB1↓, decreased pAKT expression and the β-catenin and N-cadherin epithelial-to-mesenchymal transition markers in WA-treated tumors control
N-cadherin↓,
EMT↓,
FASN↓, WA intraperitoneal administration (0.1 mg) resulted in significant suppression of circulatory free fatty acid and fatty acid synthase expression, ATP citrate lyase,
ACLY↓,
ROS↑, WA generates ROS followed by the activation of Nrf2, HO-1, NQO1 pathways, and upregulating the expression of the c-Jun-N-terminal kinase (JNK)
NRF2↑,
HO-1↑,
NQO1↑,
JNK↑,
mTOR↓, suppressing the mTOR/STAT3 pathway
neuroP↑, neuroprotective ability of WA (50 mg/kg b.w)
*TNF-α↓, WA attenuate the levels of neuroinflammatory mediators (TNF-α, IL-1β, and IL-6)
*IL1β↓,
*IL6↓,
*IL8↓, WA decreases the pro-inflammatory cytokines (IL-6, TNFα, IL-8, IL-18)
*IL18↓,
RadioS↑, radiosensitizing combination effect of WA and hyperthermia (HT) or radiotherapy (RT)
eff↑, WA and cisplatin at suboptimal dose generates ROS and causes cell death [41]. The actions of this combination is attributed by eradicating cells, revealing markers of cancer stem cells like CD34, CD44, Oct4, CD24, and CD117

943- BetA,    Betulinic acid suppresses breast cancer aerobic glycolysis via caveolin-1/NF-κB/c-Myc pathway
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vivo, NA, NA
Glycolysis↓,
lactateProd↓,
GlucoseCon↓,
ECAR↓,
cMyc↓,
LDHA↓,
p‑PDK1↓,
PDK1↓,
Cav1↑, Cav-1) as one of key targets of BA in suppressing aerobic glycolysis, as BA administration resulted in Cav-1 upregulation
*Glycolysis↑, BA could lead to increased glycolysis in mouse embryonic fibroblasts by activating LKB1/AMPK pathway, whereas we found that BA inhibited aerobic glycolysis in breast cancer cells by modulating Cav-1/NF-κB/c-Myc signaling
selectivity↑,
OCR↓, OCR parameters including the basal respiration, maximal respiration and spare respiratory capacity were also simultaneously inhibited
OXPHOS↓, implying that the activity of mitochondrial oxidative phosphorylation (OXPHOS) chain was also suppressed by BA

1593- Citrate,    Citrate Induces Apoptotic Cell Death: A Promising Way to Treat Gastric Carcinoma?
- in-vitro, GC, BGC-823 - in-vitro, GC, SGC-7901
PFK↓, citrate, a strong physiological inhibitor of phosphofructokinase (PFK)
Glycolysis↓, citrate is a strong inhibitor of glycolysis
tumCV↓, 10 mM citrate led to a nearly complete disappearance of cancer cells, and after 72 h, no cells remained viable whatever the concentration used
cl‑Casp3↑,
cl‑PARP↑,
Apoptosis↑,
ATP↓, depletion of ATP generated by citrate
ChemoSen↑, In the previous study, citrate sensitized the cells to cisplatin, a drug which was poorly efficient by itself on such cells
Mcl-1↓, In the current study, citrate reduced MCL-1 expression in both the gastric cancer lines in a dose-dependent manner, in agreement with previous observations in mesothelioma cells
glucoNG↑, citrate activates neoglucogenesis by enhancing fructose 1,6-bisphosphatase activity
FBPase↑,
OXPHOS↓, When citrate is abundant in cells, this usually means that energy production (ATP) is sufficient, so oxidative phosphorylation (OXPHOS) and the Krebs cycle are slowed down or stopped.
TCA↓, Krebs cycle are slowed down or stopped.
β-oxidation↓, concomitantly inhibits β-oxidation
HK2↓, It may inhibit HK, at least indirectly, by the physiological retroaction of glucose-6-phosphate (G6P) on HK
PDH↓, citrate may inhibit pyruvate dehydrogenase (PDH) (39), the enzyme of the Krebs cycle which links glycolysis and the tricarboxylic cycle
ROS↑, citrate could also promote the formation of reactive oxygen species (ROS) since a sudden elevation of citrate concentration inside the cell might immediately stimulate the Krebs cycle.

1583- Citrate,    Extracellular citrate and metabolic adaptations of cancer cells
- Review, NA, NA
Warburg↓, hypothesis that extracellular citrate might play a major role in cancer metabolism and is responsible for a switch between Warburg effect and OXPHOS
OXPHOS↓,
Dose∅, 10 mM citrate, cancer cells were shown to have decreased proliferation, ATP synthesis,
TumCP↓,
ATP↓,
eff↑, increased apoptosis and sensitivity to cis-platin
Apoptosis↑,
TumCG↓, high doses of citrate in vivo decreased tumour growth
PFK1↓, increased levels of cytosolic citrate taken up from the extracellular space would decrease phosphofructokinase-1 (PFK-1) activity

933- CUR,  EP,    Effective electrochemotherapy with curcumin in MDA-MB-231-human, triple negative breast cancer cells: A global proteomics study
- in-vitro, BC, NA
Apoptosis↑,
ALDOA↓,
ENO2↓,
LDHA↓, LDH inhibitor
LDHB↓,
PFKP↓,
PGK1↓,
PGM1↓,
PGAM1↓,
OXPHOS↑, upregulation of 10 oxidative phosphorylation pathway proteins
TCA↑, upregulation of 8 tricarboxylic acid (TCA) cycle proteins

1875- DCA,    Dichloroacetate inhibits neuroblastoma growth by specifically acting against malignant undifferentiated cells
- in-vitro, neuroblastoma, NA - in-vivo, NA, NA
selectivity↑, acting specifically on the mitochondria of cancer cells without perturbing the physiology of nonmalignant cells.
AntiCan↑, DCA exhibits an unexpected anticancer effect on NB tumor cells
TumVol↓, growth inhibition became statistically significant when mice were treated with 25 mg/kg/dose of DCA (55% of reduction compared with control group)
PDKs↓, effects of DCA are related to PDK inhibition, mitochondrial oxidative phosphorylation activation and specific mitochondrial hyperpolarization reduction,
mt-OXPHOS↑,
MMP↓,
Glycolysis↓, shifting cellular metabolism from glycolysis to glucose oxidation, without any deleterious effect on normal cells.
toxicity↓, Indeed, more than 40 clinical trials of DCA report that the most significant adverse effect of long-term DCA administration is a reversible peripherical neuropathy.
Warburg↓, indeed, DCA is able to reverse the Warburg effect by inhibiting PDK, restoring mitochondrial membrane potential and increasing ROS production.
ROS↑,
eff↑, DCA was celebrated as the magic bullet against cancer, even if it is currently not yet approved for cancer treatment.

5196- DCA,    Dichloroacetate induces apoptosis in endometrial cancer cells
- in-vitro, Var, NA
selectivity↑, Initiation of apoptosis was observed in five low to moderately invasive cancer cell lines including Ishikawa, RL95-2, KLE, AN3CA, and SKUT1B while treatment had no effect on non-cancerous 293T cells.
MMP↓, a decrease in mitochondrial membrane potential, and decreased Survivin transcript abundance, which are consistent with a mitochondrial-regulated mechanism.
survivin↓,
Ca+2↓, DCA treatment decreased intracellular calcium levels in most apoptotic responding cell lines which suggests a contribution from the NFAT-Kv1.5-mediated pathway.
P53↑, DCA treatment increased p53 upregulated modulator of apoptosis (PUMA) transcripts in cell lines with an apoptotic response, suggesting involvement of a p53-PUMA-mediated mechanism.
PDK1↓, DCA binds to PDK and attenuates inhibition of PDH activity.
PDH↑,
Glycolysis↓, The increased PDH activity shifts metabolism from glycolysis to glucose oxidation and decreases mitochondrial membrane potential (MMP) hyperpolarization
OXPHOS↑,
ROS↑, translocation of reactive oxygen species (ROS) and cytochrome c from the mitochondria to the cytoplasm, subsequently inducing apoptosis through the activation of caspases
Cyt‑c↑,
Apoptosis↑,
Casp↑,
tumCV↓, DCA Reduces Endometrial Cancer Cell Viability in a Dose-Dependent Manner
PUMA↑, DCA Increases PUMA Expression

4901- DCA,  Sal,    Dichloroacetate and Salinomycin as Therapeutic Agents in Cancer
- Review, NSCLC, NA
Glycolysis↓, DCA redirects mitochondrial metabolism away from glycolysis to OXPHOS by the inhibition of PDKs
OXPHOS↑,
PDKs↓,
ROS↑, DCA increases reactive oxygen species (ROS), which induce downstream changes in mitochondrial function, causing the selective apoptosis of cancer cells.
Apoptosis↑,
GlucoseCon↓, treatment with DCA decreased glucose consumption and lactate production in vitro in a manner that was statistically significant compared to the controls
lactateProd↓,
RadioS↑, it enhanced the sensitivity of A549 and H1299 cells to X-ray-induced cell killing
TumAuto↑, DCA has been shown to induce autophagy instead of inhibiting it.
mTOR↓, The DCA-induced induction of autophagy was found to be mediated by the generation of ROS, the inhibition of the mammalian targets of rapamycin (mTOR),
LC3s↓, Lu and colleagues found that LC3 decreased while p62 levels increased, both of which are hallmarks of autophagy inhibition
p62↑,
TumCG↓, In vivo studies have demonstrated that DCA inhibits the growth of A549 and H1975 tumor xenografts and enhances the survival of tumor-bearing nude mice
OS↑,
toxicity↝, the most clinically limiting side effect of DCA is peripheral neuropathy
ChemoSen↑, DCA exerts synergistic potential with the most widely used chemotherapy agent, paclitaxel, on NSCLC cells.
eff↑, DCA has also been shown to have anticancer synergies with various non-traditional agents, the most prominent of which is metformin.
eff↑, Another compound that DCA has been shown to have a strong synergism with is ivermectin.
Ferritin↓, SAL and its derivatives prevent the movement of iron from the lumen to the cytosol, triggering an iron-depletion reaction that is characterized by the rapid degradation of ferritin
CSCs↓, SAL has been shown to selectively target CSCs in vitro and in vivo, but its mode of action is not fully understood.
EMT↓, SAL has also been shown to suppress the epithelial–mesenchymal transition (EMT) as well as transforming growth factors (TGFs). EMT is a process that is pivotal to metastasis.
ROS↑, SAL triggers apoptosis by elevating intracellular ROS levels, leading to the translocation of Bax protein to the mitochondria, cytochrome c (Cytc) release, and the activation of caspase-3
Cyt‑c↑,
Casp3↑,
ER Stress↑, SAL was observed to upregulate ER stress-related proteins in a time-/dose-dependent manner
selectivity↑, SAL induced cell death in multiple apoptosis-resistant cancer cell lines, but not in normal healthy human cells
eff↑, Skeberdytė and colleagues were among the first to recognize that DCA had synergistic potential with SAL.
TumCG↓, DCA and SAL were found to significantly suppress tumor growth in vivo in the mice.

1863- dietFMD,  Chemo,    Effect of fasting on cancer: A narrative review of scientific evidence
- Review, Var, NA
eff↑, recommend combining prolonged periodic fasting with a standard conventional therapeutic approach to promote cancer‐free survival, treatment efficacy, and reduce side effects in cancer patients.
ChemoSideEff↓, lowered levels of IGF1 and insulin have the potential to protect healthy cells from side effects
ChemoSen↑,
Insulin↓, causes insulin levels to drop and glucagon levels to rise
HDAC↓, Histone deacetylases are inhibited by ketone bodies, which may slow tumor development.
IGF-1↓, FGF21 rises during intermittent fasting, and it plays a vital role in lowering IGF1 levels by inhibiting phosphorylated STAT5 in the liver
STAT5↓,
BG↓, Fasting suppresses glucose, IGF1, insulin, the MAPK pathway, and heme oxygenase 1
MAPK↓,
HO-1↓,
ATG3↑, while increasing many autophagy‐regulating components (Atgs, LC3, Beclin1, p62, Sirt1, and LAMP2).
Beclin-1↑,
p62↑,
SIRT1↑,
LAMP2↑,
OXPHOS↑, Fasting causes cancer cells to release oxidative phosphorylation (OXPHOS) through aerobic glycolysis
ROS↑, which leads to an increase in reactive oxygen species (ROS), p53 activation, DNA damage, and cell death in response to chemotherapy.
P53↑,
DNAdam↑,
TumCD↑,
ATP↑, and causes extracellular ATP accumulation, which inhibits Treg cells and the M2 phenotype while activating CD8+ cytotoxic T cells.
Treg lymp↓,
M2 MC↓,
CD8+↑,
Glycolysis↓, By lowering glucose intake and boosting fatty acid oxidation, fasting can induce a transition from aerobic glycolysis to mitochondrial oxidative phosphorylation in cancerous cells, resulting in increased ROS
GutMicro↑, Fasting has been shown to have a direct impact on the gut microbial community's constitution, function, and interaction with the host, which is the complex and diverse microbial population that lives in the intestine
GutMicro↑, Fasting also reduces the number of potentially harmful Proteobacteria while boosting the levels of Akkermansia muciniphila.
Warburg↓, Fasting generates an anti‐Warburg effect in colon cancer models, which increases oxygen demand but decreases ATP production, indicating an increase in mitochondrial uncoupling.
Dose↝, Those patients fasted for 36 h before treatment and 24 h thereafter, having a total of 350 calories per day. Within 8 days of chemotherapy, no substantial weight loss was recorded, although there was an improvement in quality of life and weariness.

1853- dietFMD,    Impact of Fasting on Patients With Cancer: An Integrative Review
- Review, Var, NA
*toxicity∅, Data suggest overall good compliance, no malnutrition, minimal side effects. No significant changes were identified to suggest increased harm.
QoL∅, unchanged quality of life (QOL),
eff↑, improved endocrine parameters
eff↝, mixed results for cancer outcomes
ChemoSideEff↓, decreasing chemotherapy-related side effects
TumCG↓, limiting tumor growth
Dose↑, When fasting is used as an adjunct to chemotherapy, a minimum fasting period of at least 48 hours is currently recommended for nutritional interventions in order to achieve a measurable metabolic response at the cellular level
toxicity↝, The increased risk for poor outcomes associated with malnutrition, weight loss, and cachexia poses an obvious safety concern for patients with cancer who participate in calorie-restricted fasting
eff↑, short-term fasting involving water-only or limited daily calorie consumption for less than a week has the potential to achieve positive metabolic changes while avoiding malnutrition and significant weight loss
IGF-1↑, statistically significant decrease in IGF-1 among participants compliant with fasting compared with regular diet during the middle of therapy
*OXPHOS↑, Healthy cells also use mitochondrial oxidative phosphorylation for metabolism while cancer cells use aerobic glycolysis, also known as the Warburg effect
BG↓, statistically significant decrease in glucose among participants compliant with fasting compared with controls
Insulin↓, statistically significant decrease in insulin among participants compliant with fasting compared with regular diet before the first cycle of chemotherapy (p = .001), as well as during the middle of therapy
RadioS↑, A complete or partial radiographic response was also noted more often among fasting participants compared with normal diet participants

1854- dietFMD,    How Far Are We from Prescribing Fasting as Anticancer Medicine?
- Review, Var, NA
ChemoSideEff↓, ample nonclinical evidence indicating that fasting can mitigate the toxicity of chemotherapy and/or increase the efficacy of chemotherapy.
ChemoSen↑, Fasting-Induced Increase of the Efficacy of Chemotherapy
IGF-1↓,
IGFBP1↑, biological activity of IGF-1 is further compromised due to increased levels of insulin-like growth factor binding protein 1 (IGFBP1)
adiP↑, increased levels of adiponectin stimulate the fatty acid breakdown.
glyC↓, After depletion of stored glycogen, which occurs usually 24 h after initiation of fasting, the fatty acids serve as the main fuels for most tissues
E-cadherin↑, upregulation of E-cadherin expression via activation of c-Src kinase
MMPs↓, decrease of cytokines, chemokines, metalloproteinases, growth factors
Casp3↑, increase of level of activated caspase-3
ROS↑, it is postulated that the beneficial effects of fasting are ascribed to rapid metabolic and immunological response, triggered by a temporary increase in oxidative free radical production
ATP↓, Glucose deprivation leads to ATP depletion, resulting in ROS accumulation
AMPK↑, Additionally, ROS activate AMPK
mTOR↓, Under conditions of glucose deprivation, AMPK inhibits mTORC1
ROS↑, Beyond glucose deprivation, another mechanism increasing ROS levels is the AA (amino acids) starvation
Glycolysis↓, Indeed, in cancer cells, limited glucose sources impair glycolysis, decrease glycolysis-based NADPH production due to reduced utilization of the pentose phosphate pathway [88,89,90,91],
NADPH↓,
OXPHOS↝, and shift the metabolism from glycolysis to oxidative phosphorylation (OXPHOS) (“anti-Warburg effect”), leading to ROS overload [92,93,94,95].
eff↑, Fasting compared to long-term CR causes a more profound decrease in insulin (90% versus 40%, respectively) and blood glucose (50% versus 25%, respectively).
eff↑, FMD have been demonstrated to result in alterations of the serum levels of IGF-I, IGFBP1, glucose, and ketone bodies reminiscent of those observed in fasting
*RAS↓, A plausible explanation of the differential protective effect of fasting against chemotherapy is the attenuation of the Ras/MAPK and PI3K/Akt pathways downstream of decreased IGF-1 in normal cells
*MAPK↓,
*PI3K↓,
*Akt↓,
eff↑, Starvation combined with cisplatin has been shown in vitro to protect normal cells, promoting complete arrest of cellular proliferation mediated by p53/p21 activation in AMPK-dependent and ATM-independent manner
ROS↑, generation of ROS due to paradoxical activation of the AKT/S6K, partially via the AMPK-mTORC1 energy-sensing pathways malignant cells
Akt↑, cancer cells
Casp3↑, combination of fasting and chemotherapy was in part ascribed to enhanced apoptosis due to activation of caspase 3

5069- dietSTF,    The Role of Intermittent Fasting in the Activation of Autophagy Processes in the Context of Cancer Diseases
- Review, Var, NA
Risk↓, IF has shown potential for reducing cancer risk and enhancing therapeutic efficacy by sensitizing tumor cells to chemotherapy and radiotherapy.
ChemoSen↑, intermittent fasting (IF) may enhance the effectiveness of chemotherapy and targeted therapies by activating autophagy. IF enhances the effectiveness of chemotherapy, including drugs such as cisplatin, cyclophosphamide, and doxorubicin
RadioS↑, disease stabilization, improved response to radiotherapy patients with glioma
*Dose↝, 16:8—16 h of fasting with an 8 h eating window;
*Dose↝, 5:2—consuming a standard number of calories for 5 days and reducing intake to 25% of daily requirements for 2 days;
*Dose↝, Eat–Stop–Eat—complete fasting for 24–48 h.
*LDL↓, IF during Ramadan (approximately 18 h of fasting for 29–30 days) reduces LDL cholesterol levels and increases HDL cholesterol in women, as well as reducing inflammatory markers such as CRP and TNF-α
*CRP↓,
*TNF-α↓,
TumAuto↓, Intermittent fasting activates autophagy as an adaptive mechanism to nutrient deprivation, which may modulate tumor development and treatment
GLUT1↓, fasting reduces the expression of glucose transporters GLUT1/2, which slow down cancer metabolism and increase the susceptibility of cancer cells to oxidative stress
GLUT2↓,
glucose↓, studies on cell and animal models have shown that intermittent fasting reduces glucose and insulin-like growth factor (IGF-1) levels [103], as well as insulin [104,105], resulting in the inhibition of the mTOR kinase pathway (PI3K/Akt/mTOR), suppress
IGF-1↓,
Insulin↓,
mTOR↓,
mTORC1↓, suppression of mTORC1 [22], and activation of AMPK through increased ADP/ATP ratio in cells, which supports autophagy and induces apoptosis
AMPK↑,
Warburg↓, Moreover, IF counteracts the Warburg effect by promoting oxidative phosphorylation, leading to an increase in the production of reactive oxygen species (ROS) and enhanced oxidative stress in cancer cells [106,108], causing DNA damage and the activati
OXPHOS↑,
ROS↑,
DNAdam↑,
JAK1↓, fasting reduces the production of adenosine by cancer cells, inhibiting the activation of the JAK1/STAT pathway, thereby reducing cancer cell proliferation
STAT↓,
TumCP↓,
QoL↑, reduction in IGF-1 levels, improved quality of life patients with multiple cancer types

694- EGCG,    Matcha green tea (MGT) inhibits the propagation of cancer stem cells (CSCs), by targeting mitochondrial metabolism, glycolysis and multiple cell signalling pathways
- in-vitro, BC, MCF-7
Glycolysis↓, MGT might similarly act as a glycolysis inhibitor
GAPDH↓,
ROS↑, Tea cathechins may act both as anti-oxidant and as pro-oxidants
OCR↓,
ECAR↓,
mTOR↓,
OXPHOS↓,

2310- EGCG,    Epigallocatechin-3-gallate downregulates PDHA1 interfering the metabolic pathways in human herpesvirus 8 harboring primary effusion lymphoma cells
- in-vitro, lymphoma, PEL
GLUT3↑, EGCG increased GLUT3 and decreased PDHA1 and GDH1 expression to disrupt glycolysis and glutaminolysis in PEL cells
PDHA1↓,
GDH↓,
ROS↑, Previously we have demonstrated that EGCG induces ROS generation and cell death in HHV8 harboring PEL cells
Glycolysis↓, EGCG induced PEL cell death may due to suppresses both the aerobic glycolysis and oxidative phosphorylation
OXPHOS↓,

2512- H2,    Hydrogen Attenuates Allergic Inflammation by Reversing Energy Metabolic Pathway Switch
- in-vivo, asthmatic, NA
selectivity↑, we treated mice with HRS for 7 days. HRS had no effects on OXPHOS and glycolytic activities in control mice
lactateProd↓, but prevented the elevation in lactate and reduction in ATP production in lungs of OVA-sensitized and challenged mice
ATP↑,
HK2↓, Consistently, HRS attenuated the increase in HK and PFK activities
PFK↓,
Hif1a↓, OVA sensitization and challenge increased HIF-1α nuclear translocation (stimulated HIF-1α activity), which was inhibited by HRS treatment
PGC-1α↑, By contrast, OVA sensitization and challenge downregulated PGC-1α protein expression, and HRS treatment reversed this downregulation
Glycolysis↓, H2 reverses energy metabolic switch by inhibiting glycolytic enzyme activities and by stimulating mitochondrial OXPHOS enzyme activities
OXPHOS↑,
Dose↝, HRS was prepared by dipping a plastic-shelled stick consisting of metallic magnesium (99.9% pure) and natural stones (Doctor SUISOSUI, Friendear Inc., Tokyo, Japan) into sterilized saline.

2071- HNK,    Identification of senescence rejuvenation mechanism of Magnolia officinalis extract including honokiol as a core ingredient
- Review, Nor, HaCaT
*ROS↓, Magnolia officinalis (M. officinalis) extract significantly lowered the levels of ROS in senescent fibroblasts.
*antiOx↑, honokiol was demonstrated as a core ingredient of M. officinalis extract that exhibits antioxidant effects.
*AntiAge↑, new approaches to anti–aging treatments
*MMP↑, increases MMP
*ECAR↓, senescent fibroblasts treated with M. officinalis extract had lower ECAR values than those treated with DMSO, suggesting that M. officinalis treatment lowed glycolysis rate
*Glycolysis↓, honokiol, similar to M. officinalis, reduced the dependence of glycolysis as an energy source, indicating restoration of mitochondrial function by honokiol.
*PAR-2↓, downregulation of PAR–2 expression by M. officinalis may reduce skin pigmentation.
*CXCL12↑, upregulation of SDF–1 expression by M. officinalis may reduce skin pigmentation.
*BMAL1↑, activation of Bmal–1 expression by M. officinalis promote skin turnover.
*mt-ROS↓, compared to M. officinalis extract, honokiol at 1 and 10 μM was more effective in lowering mitochondrial ROS levels
*OXPHOS↓, Inhibition of oxidative phosphorylation and induction of a compensatory shift toward glycolysis resulted in lower compensatory glycolysis in honokiol–treated senescent fibroblasts

2887- HNK,    Honokiol Restores Microglial Phagocytosis by Reversing Metabolic Reprogramming
- in-vitro, AD, BV2
*Glycolysis↑, switch from oxidative phosphorylation to anaerobic glycolysis and enhancing ATP production.
*ATP↑,
*ROS↓, honokiol reduced mitochondrial reactive oxygen species production and elevated mitochondrial membrane potential.
*MMP↑,
*OXPHOS↑, Honokiol enhanced ATP production by promoting mitochondrial OXPHOS in BV2 cell
*PPARα↑, Therefore, we argue that honokiol increases the expression of PPAR and PGC1, thus regulating a metabolic switch from glycolysis to OXPHOS
*PGC-1α↑,

886- HPT,    Impact of hyper- and hypothermia on cellular and whole-body physiology
- Analysis, NA, NA
MMP↓,
OXPHOS↓, impaired oxidative phosphorylation
ATP↓,
ROS↑, increase reactive oxygen species (ROS) production within mitochondria,
Apoptosis↑,
Cyt‑c↑, releasing cytochrome c into the cytoplasm

2543- M-Blu,    The use of methylene blue to control the tumor oxygenation level
- in-vivo, Lung, NA
OCR↑, A concentration of 10 mg/kg resulted in a relative increase of the tumor oxygenation level for small tumors (volume 50–75 mm3) and normal tissue 120 min after the introduction of MB
OXPHOS↑, A shift in tumor metabolism towards oxidative phosphorylation (according to the lifetime of the NADH coenzyme) was measured using FLIM method after intravenous administration of 10 mg/kg of MB
Half-Life↝, persisted for at least 120 min after the administration and did not return to its initial level.
AntiTum↑, B therapy enhances tumor oxygenation levels, which contributes to more effective antitumor therapy.

2541- M-Blu,    Spectroscopic Study of Methylene Blue Interaction with Coenzymes and its Effect on Tumor Metabolism
- in-vivo, Var, NA
TumCG↓, In the group receiving MB with drinking water, a decrease of the tumor growth rate, reduction of oxygenation level, and a1/a2 metabolic index were observed, which confirms the shift from glycolysis to oxidative phosphorylation.
Glycolysis↓,
OXPHOS↑,
ROS↑, The ability of MB to generate reactive oxygen species together with a small molecular size makes this dye attractive for using it as a photosensitizer in photodynamic therapy
OCR↑, MB can increase oxygen consumption, decrease glycolysis and increase glucose uptake in vitro
GlucoseCon↑,
lactateProd↓, The decrease of the lactate amount and extracellular acidification rate after MB introduction, which is reported in the literature [31], is supposed to be a secondary effect mediated by the metabolic shift towards oxidation phosphorylation as a resul

2540- M-Blu,    Alternative mitochondrial electron transfer for the treatment of neurodegenerative diseases and cancers: Methylene blue connects the dots
- Review, Var, NA - Review, AD, NA
*OCR↑, MB was found to increase oxygen consumption of normal tissues having aerobic glycolysis and of tumors
*Glycolysis↓, Methylene blue increases oxygen consumption, decrease glycolysis, and increases glucose uptake in vitro.
*GlucoseCon↑, Methylene blue enhances glucose uptake and regional cerebral blood flow in rats upon acute treatment.
neuroP↑, methylene blue provides protective effect in neuron and astrocyte against various insults in vitro and in rodent models of Alzheimer’s, Parkinson’s, and Huntington’s disease.
Warburg↓, In glioblastoma cells, methylene blue reverses Warburg effect by enhancing mitochondrial oxidative phosphorylation, arrests glioma cell cycle at s-phase, and inhibits glioma cell proliferation.
mt-OXPHOS↑,
TumCCA↑,
TumCP↓,
ROS⇅, MB has very unique redox property that exists in equilibrium between oxidized state in dark blue (MB) and colorless reduced state (leucomethylene blue), making it both prooxidant and antioxidant under different conditions.
*cognitive↑, Methylene blue feeding improved water-maze and bridge walking performance in 5 X FAD mice. MB enhances memory function in normal rodents potentially through neurometabolic mechanisms
*mTOR↓, MB has been demonstrated to induce autophagy and attenuate tauopathy through inhibition of mTOR signaling both in vitro and in vivo
*mt-antiOx↑, Secondly, the distinct redox property enables MB as a regenerable anti-oxidant in mitochondria that distinct from the traditional free radical scavenges
*memory↑, , MB has been found to improve various experimental memory tasks in rodents
*BBB↑, MB can cross BBB and reach brain at concentrations 10 times higher than that in the circulation
*eff↝, In fibroblast cells, MB has been shown to stimulate 2-deoxyglucose uptake (Louters et al., 2006; Roelofs et al., 2006). Using MRI and PET, we demonstrated that acute treatment of MB significantly enhance glucose uptake
*ECAR↓, MB increased oxygen consumption rate and decreased extracellular acidification rate in both neuronal cells and astrocytes
eff↑, MB has also been used as a tracer for cancer diagnosis and as a photosensitizer for cancer treatment
lactateProd↓, MB increase oxygen consumption rate, decrease lactic acid production and extracellular acidification rate, reduce NADPH, and inhibit proliferation
NADPH↓,
OXPHOS↑, increases oxidative phosphorylation, decreases glycolytic flux and metabolic intermediates, hence, exhausts the building brick for cancer cell proliferation.
AMPK↑, MB is capable of activating AMPK signal pathway
selectivity↑, with low toxicity, and the high affinity to both neuronal and cancer tissues

1198- MAG,    Mitochondria-targeted magnolol inhibits OXPHOS, proliferation, and tumor growth via modulation of energetics and autophagy in melanoma cells
- in-vivo, Melanoma, NA
OXPHOS↓, 100fold: Mito-magnolol (Mito-MGN), inhibits oxidative phosphorylation (OXPHOS) and proliferation of melanoma cells more potently than untargeted magnolol
TumCP↓,

2384- MET,    Integration of metabolomics and transcriptomics reveals metformin suppresses thyroid cancer progression via inhibiting glycolysis and restraining DNA replication
- in-vitro, Thyroid, BCPAP - in-vivo, NA, NA - in-vitro, Thyroid, TPC-1
Glycolysis↓, Metformin promotes the metabolic transition from glycolysis to oxidative phosphorylation.
OXPHOS↑,
tumCV↓, metformin reduced cell viability, invasion, migration, and EMT, and induced apoptosis and cell cycle G1 phase arrest in thyroid cancer.
TumCI↓,
TumCMig↓,
EMT↓,
Apoptosis↑,
TumCCA↑, cell cycle G1 phase
LDHA↓, metformin suppressed glycolysis by downregulating the key glycolytic enzymes LDHA and PKM2 and upregulating IDH1 expression in thyroid cancer.
PKM2↓,
IDH1↑,
TumCG↓, Metformin inhibits the growth of thyroid cancer in vivo

2242- MF,    Electromagnetic stimulation increases mitochondrial function in osteogenic cells and promotes bone fracture repair
- in-vitro, Nor, NA
*MMP↑, we show that application of a low intensity constant EM field source on osteogenic cells in vitro resulted in increased mitochondrial membrane potential and respiratory complex I activity and induced osteogenic differentiation.
*Diff↑,
*OXPHOS↑, effect was mediated via increased OxPhos activity
*BMD↑, EM field source enhanced fracture repair via improved biomechanical properties and increased callus bone mineralization
ATP∅, higher mitochondrial OxPhos activity leads to higher ATP production, increased cellular activity leads to increased ATP consumption.

2249- MF,    Pulsed electromagnetic fields modulate energy metabolism during wound healing process: an in vitro model study
- in-vitro, Nor, L929
*TumCMig↑, PEMFs with specific parameter (4mT, 80 Hz) promoted cell migration and viability.
*tumCV↑,
*Glycolysis↑, PEMFs-exposed L929 cells was highly glycolytic for energy generation
*ROS↓, PEMFs enhanced intracellular acidification and maintained low level of intracellular ROS in L929 cells.
*mitResp↓, shifting from mitochondrial respiration to glycolysis
*other↝, Furthermore, the analysis of ECAR/ OCR basal ratio demonstrated a tendency toward to glycolytic phenotype in L929 cells under PEMF exposure, compared to control group
*OXPHOS↓, PEMFs promoted the transformation of energy metabolism pattern from oxidative phosphorylation to aerobic glycolysis
*pH↑, result of pH detection by flow cytometer indicated the pH level in L929 cells was significantly increased in the PEMFs group compared to the control group
*antiOx↑, PEMFs upregulated the expression of antioxidant or glycolysis related genes
*PFKM↑, Pfkm, Pfkl, Pfkp, Pkm2, Hk2, Glut1, were also significantly up-regulated in the PEMFs group
*PFKL↑,
*PKM2↑,
*HK2↑,
*GLUT1↑,
*GPx1↑, GPX1, GPX4 and Sod 1 expression were significantly higher in the PEMFs group compared to the control group
*GPx4↑,
*SOD1↑,

2241- MF,    Pulsed electromagnetic therapy in cancer treatment: Progress and outlook
- Review, Var, NA
other↝, PEMFs act on the cell, it will firstly change the cell membrane transport capacity, osmotic potential and ionic valves
p‑ERK↝, Also, it will cause changes in mitochondrial protein profile, decrease mitochondrial phosphor-ERK (extracellular-signal-regulated kinase), p53, and cytochrome c, and activate OxPhos.
P53↝,
Cyt‑c↝,
OXPHOS↑,
Apoptosis↑, PEMFs decreases cellular stress factors, increase energy demand, this series of reactions will eventually lead to apoptosis.
ROS↑, The introduction of PEFs and PEMFs can improve the penetration efficiency of ROS, not only reduce the concentration of drugs, but also reduce the irradiation dose of CAP, w

2247- MF,    Effects of Pulsed Electromagnetic Field Treatment on Skeletal Muscle Tissue Recovery in a Rat Model of Collagenase-Induced Tendinopathy: Results from a Proteome Analysis
- in-vivo, Nor, NA
*Glycolysis↓, PEMF-treated animals exhibited decreased glycolysis and increased LDHB expression, enhancing NAD signaling and ATP production
*LDHB↑,
*NAD↑,
*ATP↑,
*antiOx↑, Antioxidant protein levels increased, controlling ROS production.
*ROS↑,
*YAP/TEAD↑, upregulation of YAP and PGC1alpha and increasing slow myosin isoforms, thus speeding up physiological recovery.
*PGC-1α↑,
*TCA↑, increased in PEMF-treated injured limbs
*FAO↑,
*OXPHOS↑, Oxidative phosphorylation was increased in the muscle of injured rats that underwent PEMF treatment

2260- MF,    Alternative magnetic field exposure suppresses tumor growth via metabolic reprogramming
- in-vitro, GBM, U87MG - in-vitro, GBM, LN229 - in-vivo, NA, NA
TumCP↓, proliferation of human glioblastoma multiforme (GBM) cells (U87 and LN229) was inhibited upon exposure to AMF within a specific narrow frequency range, including around 227 kHz.
TumCG↓, daily exposure to AMF for 30 min over 21 days significantly suppressed tumor growth and prolonged overall survival
OS↑,
ROS↑, This effect was associated with heightened reactive oxygen species (ROS) production and increased manganese superoxide dismutase (MnSOD) expression.
SOD2↑,
eff↓, anti-cancer efficacy of AMF was diminished by either a mitochondrial complex IV inhibitor or a ROS scavenger.
ECAR↓, decrease in the extracellular acidification rate (ECAR) and an increase in the oxygen consumption rate (OCR).
OCR↑,
selectivity↑, This suggests that AMF-induced metabolic reprogramming occurs in GBM cells but not in normal cells. Furthermore, in cancer cells, AMF decreased ECAR and increased OCR, while there were no changes in normal cells.
*toxicity∅, did not affect non-cancerous human cells [normal human astrocyte (NHA), human cardiac fibroblast (HCF), human umbilical vein endothelial cells (HUVEC)].
TumVol↓, The results showed a significant treatment effect, as assessed by tumor volume, after conducting AMF treatment five times a week for 2 weeks
PGC-1α↑, Corresponding to the rise in ROS, there was also a time-dependent increase in PGC1α protein expression post-AMF exposure
OXPHOS↑, enhancing mitochondrial oxidative phosphorylation (OXPHOS), leading to increased ROS production
Glycolysis↓, metabolic mode of cancer cells to shift from glycolysis, characteristic of cancer cells, toward OXPHOS, which is more typical of normal cells.
PKM2↓, We extracted proteins that changed commonly in U87 and LN229 cells. Among the individual proteins related to metabolism, pyruvate kinase M2 (PKM2) was found to be inhibited in both.

538- MF,    The extremely low frequency electromagnetic stimulation selective for cancer cells elicits growth arrest through a metabolic shift
- in-vitro, BC, MDA-MB-231 - in-vitro, Melanoma, MSTO-211H
TumCG↓, did not affect the non-malignant counterpart.
Ca+2↑,
COX2↓,
ATP↑, (ATP5B) and mitochondrial transcription (MT-ATP6)
MMP↑, significant enhancement of mitochondrial membrane potential (ΔΨm)
ROS↑, demonstrated for the first time the association of ROS production with the stimulation of the mitochondrial metabolism triggered by the electromagnetic field
OXPHOS↑,
mitResp↑, Mitochondrial respiration is increased by ELF-EMF exposure

525- MF,    Pulsed electromagnetic fields regulate metabolic reprogramming and mitochondrial fission in endothelial cells for angiogenesis
- in-vitro, Nor, HUVECs
*angioG↑, PEMFs promoted a shift in the energy metabolism pattern of HUVECs from oxidative phosphorylation to aerobic glycolysis.
*GPx1↑, 4x
*GPx4↑, 2.2x
*SOD↑, SOD1/2 3.5x
*PFKM↑, 3x
*PFKL↑, 2.5x
*PKM2↑, 2.6x : activation of PKM2 enhanced angiogenesis in endothelial cells (ECs) by modulating glycolysis, mitochondrial fission, and fusion
*PFKP↑, 2.8x
*HK2↑, 4x
*GLUT1↑, 1.5x
*GLUT4↑, 1.6x
*ROS↓, reminder: normal HUVECs cells
*MMP↝, no damage, (normal cells)
*Glycolysis↑, (PFKL, PFKLM, PFKP, PKM2, and HK2) encoding the three key regulatory enzymes of glycolysis, hexokinase, phosphofructokinase, and pyruvate kinase, sharply increased when HUVECs were exposed to PEMFs
*OXPHOS↓, PEMFs promoted a shift in the energy metabolism pattern of HUVECs from oxidative phosphorylation to aerobic glycolysis

2396- PACs,    PKM2 is the target of proanthocyanidin B2 during the inhibition of hepatocellular carcinoma
- in-vitro, HCC, HCCLM3 - in-vitro, HCC, SMMC-7721 cell - in-vitro, HCC, Bel-7402 - in-vitro, HCC, HUH7 - in-vitro, HCC, HepG2 - in-vitro, Nor, L02
TumCP↓, PB2 inhibited the proliferation, induced cell cycle arrest, and triggered apoptosis of HCC cells in vivo and in vitro.
TumCCA↓,
Apoptosis↑,
GlucoseCon↓, PB2 also suppressed glucose uptake and lactate levels via the direct inhibition of the key glycolytic enzyme, PKM2.
lactateProd↓,
PKM2↓,
Glycolysis↓, to suppress aerobic glycolysis
HK2↓, PB2 suppressed the expression of HK2, PFKFB3, and PKM2, while enhancing the expression of OXPHOS in both HCC-LM3 and SMMC-7721 cells
PFK↓,
OXPHOS↑, PB2 inhibited aerobic glycolysis and improved OXPHOS in HCC cell lines
ChemoSen↑, PB2 enhanced the chemosensitivity of SORA on HCC, both in vivo and in vitro
HSP90↓, PB2 reduced the expressions of both HSP90 and HIF-1α in a dose-dependent manner in HCC cells
Hif1a↓,

4946- PEITC,    Phenethyl Isothiocyanate Inhibits Oxidative Phosphorylation to Trigger Reactive Oxygen Species-mediated Death of Human Prostate Cancer Cells
- in-vitro, Pca, LNCaP - in-vitro, Pca, PC3
Apoptosis↑, inhibits growth of human cancer cells by causing apoptotic and autophagic cell death.
TumAuto↑,
ROS↑, we demonstrate that the PEITC-induced cell death is initiated by production of reactive oxygen species (ROS) resulting from inhibition of oxidative phosphorylation (OXPHOS)
OXPHOS↓,
ATP↓, , suppression of OXPHOS, and ATP depletion.
selectivity↑, These effects were not observed in a representative normal human prostate epithelial cell line (PrEC)
ETC↓, PEITC-induced cell death involving ROS production due to inhibition of complex III and OXPHOS.
eff↓, PEITC-mediated increase in CM· signal intensity in PC-3 cells was markedly suppressed in the presence of NAC
eff↓, Rho-0 Variants of LNCaP and PC-3 Cells Were Resistant to PEITC-induced Apoptosis
BAX↑, PEITC Treatment Caused Mitochondrial Translocation of Bax

1991- PTL,    A novel SLC25A1 inhibitor, parthenolide, suppresses the growth and stemness of liver cancer stem cells with metabolic vulnerability
- in-vitro, Liver, HUH7
TumCCA↑, PTL stimulated cell cycle arrest at the G1 phase, induced apoptosis, and decreased the stemness of LCSCs
Apoptosis↑,
CSCs↓,
ROS↑, PTL caused the production of ROS and the reduction of oxidative phosphorylation (OXPHOS) and mitochondrial membrane potential (MMP) levels of LCSCs
OXPHOS↓, PTL inhibited OXPHOS levels
MMP↓,
SLC25A1↓, PTL decreased SLC25A1 expression at the mRNA level
IDH2↓, inhibition of SLC25A1 synergistically decreased the expression of IDH2

889- QC,    The multifaceted role of quercetin derived from its mitochondrial mechanism
- vitro+vivo, Var, NA
MMP↓,
ATP↝,
OXPHOS↝,
ROS↑, a prooxidant effect

993- RES,    Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells
- in-vitro, CRC, Caco-2 - in-vivo, Nor, HCEC 1CT
TumCG↓,
Glycolysis↓,
PPP↓,
ATP↑, significant increase (20%) in ATP production
PDH↑, Resveratrol targets the pyruvate dehydrogenase (PDH) complex, a key mitochondrial gatekeeper of energy metabolism, leading to an enhanced PDH activity.
Ca+2↝, resveratrol is a potent modulator of many cellular Ca2+ signaling pathways. Ca2+ is a key mediator of the effect of resveratrol on the oxidative capacity of colon cancer cells.
TumCP↓,
lactateProd↓,
OCR↑, increase of oxygen consumption rate (OCR) both in normal colonic epithelial HCEC 1CT cells
ECAR↓, Following treatment with resveratrol (10 µM, 48 hr), the ECAR was unchanged in normal HCEC 1CT cells, whereas it was significantly reduced (31%) in HCEC 1CT RPA cells ****
*ECAR∅, Following treatment with resveratrol (10 µM, 48 hr), the ECAR was unchanged in normal HCEC 1CT cells
*other?, Resveratrol promotes a shift from respiration to glycolysis in cancer-like cells, but not in normal colonocytes
cycE/CCNE↑, Resveratrol inhibited cell cycle progression by enhancing the levels of cyclin E and cyclin A
cycA1/CCNA1↑,
TumCCA↑,
cycD1/CCND1↑, and by decreasing cyclin D1
OXPHOS↑, Taken together, these observations indicate that exposure to resveratrol leads to a metabolic reorientation from aerobic glycolysis toward OXPHOS.

3087- RES,    Resveratrol cytotoxicity is energy-dependent
- Review, Var, NA
OXPHOS↓, The inhibition of the oxidative phosphorylation (OXPHOS) pathway appears to be the molecular mechanism of resveratrol.
eff↝, This review suggests that investigating a possible complex relationship between caloric intake and the differential effects of resveratrol on OXPHOS may be justified.
eff↑, A low-calorie diet accompanied by significant levels of resveratrol might modify cellular bioenergetics, which could impact cellular viability and enhance the anti-cancer properties of resveratrol.

3935- RT,    Sodium rutin ameliorates Alzheimer's disease-like pathology by enhancing microglial amyloid-β clearance
- in-vivo, AD, NA
*Aβ↓, rutin enhances microglial Aβ clearance, providing a potential therapeutic avenue for Alzheimer’s disease treatment.
*Glycolysis↓, NaR promotes a metabolic switch from anaerobic glycolysis to mitochondrial OXPHOS (oxidative phosphorylation), which could provide microglia with sufficient energy (ATP) for Aβ clearance.
*OXPHOS↑,
*memory↑, eventually reversing spatial learning and memory deficits. Our findings suggest that NaR is a potential therapeutic agent for AD.
*BioAv↓, poor solubility in aqueous media (approximately 0.125 g/liter at room temperature) has largely limited its usage owing to its poor bioavailability
*BioAv↑, In the present study, we processed rutin into sodium salt [hereafter called sodium rutin (NaR)], which is highly water soluble and bioavailable.
*cognitive↑, NaR ameliorates learning and memory deficits and rescues synaptic impairment in mouse models of AD
*Inflam↓, NaR decreases neuroinflammation in AD mice

4903- Sal,    Salinomycin: A new paradigm in cancer therapy
- Review, Var, NA
TumCG↓, multiple pathways by which salinomycin inhibits tumor growth
ATP↓, Salinomycin decreases the expression of adenosine triphosphate–binding cassette transporter in multidrug resistance cells
CSCs↓, Salinomycin selectively targets cancer stem cells.
ROS↑, inhibited growth and migration of prostate cancer cells,37 and led to reactive oxygen species (ROS) accumulation in androgen-dependent and independent prostate cancer cells.
Casp↑, via caspase activation and destabilization of mitochondrial membrane potential
MMP↓,
selectivity↑, Salinomycin also acted on OVCAR-3 human ovarian cancer cells through caspase-mediated apoptosis without harming normal cells
OXPHOS↓, Salinomycin inhibited mitochondrial oxidative phosphorylation without affecting the substrate-level phosphorylation.
STAT3↓, CSC population was inhibited by STAT3 down-regulation
P53↑, Salinomycin increased tumor-suppressor protein p53 and DNA damaging protein pH2AX and decreased cyclin D1 level, which led to cell-cycle arrest and high DNA damage.
γH2AX↑,
cycD1/CCND1↓,
TumCCA↑,
DNAdam↑,
ChemoSen↑, Salinomycin works synergistically with conventional chemotherapeutic drugs to inhibit invasion and migration of cancer cells.

4905- Sal,    Salinomycin as a drug for targeting human cancer stem cells
- Review, Var, NA
CSCs↓, Salinomycin, a polyether ionophore antibiotic isolated from Streptomyces albus, has been shown to kill CSCs in different types of human cancers,
selectivity↑, Salinomycin has been shown to induce massive apoptosis in acute T-cell leukemia cells [125] and chronic lymphocytic leukemia cells [126] isolated from leukemia patients but failed to induce apoptosis in normal human T cells
Apoptosis↑, salinomycin induces apoptosis in CSCs of different origin
Casp3↑, salinomycin has been shown to activate the mitochondrial pathway of apoptosis and the caspase-3-mediated cleavage of PARP in human PC-3 prostate cancer cells
ROS↑, Salinomycin is able to generate reactive oxygen species (ROS) in prostate cancer cells
Wnt↓, downregulating the expression of the Wnt target genes LEF1, cyclin D1, and fibronectin, finally leading to apoptosis
cycD1/CCND1↓,
Fibronectin↓,
OXPHOS↓, salinomycin is known to inhibit oxidative phosphorylation in mitochondria [144] that may contribute to the elimination of CSCs by salinomycin.
Diff↑, salinomycin is able to promote differentiation of CSCs
Dose↝, the patient received 12 intravenous administrations of 200 μg·kg−1 salinomycin every second day.

4906- Sal,    A Concise Review of Prodigious Salinomycin and Its Derivatives Effective in Treatment of Breast Cancer: (2012–2022)
- Review, BC, NA
CSCs↓, Salinomycin (SAL), a polyether ionophore antibiotic being used in the poultry industry, was identified as a powerful anti-cancer compound that possesses broad-spectrum activities, especially against CSCs.
Casp3↑, SAL has been shown to affect the mitochondria, leading to caspase-3 cleaving poly-ADP ribose polymerase (PARP), resulting in apoptosis.
cl‑PARP↝,
Apoptosis↑,
ROS↑, SAL has shown the ability to affect prostate cancer (PC-3) cell lines through the production of reactive oxygen species (ROS), leading to programmed cell death.
ABC↓, potential use of SAL as an ABC transporter inhibitor
OXPHOS↓, Inhibition of Oxidative Phosphorylation and Glycolysis
Glycolysis↓,
eff↑, SAL in combination with glucose analogs (2-DG, 2-FDG) increased the toxicity of SAL towards cancer cells and showed that cancer cells are dependent on glycolysis for ATP production
TumAuto↑, Induction of Autophagy, ROS, and DNA Damage
DNAdam↑,
Wnt↓, Inhibition of the Wnt Signaling Cascade
Ferritin↓, SAL was tested, and at 0.5 μM iron accumulation in the lysosome, a reduction in iron keeper ferritin expression and elevated iron regulatory protein-2 (IRP2) were observed
Iron↑, a novel mechanism of action of SAL affecting breast CSCs is iron accumulation in the lysosome. and an increased amount of iron in the lysosome produces ROS, which leads to apoptosis

3195- SFN,    AKT1/HK2 Axis-mediated Glucose Metabolism: A Novel Therapeutic Target of Sulforaphane in Bladder Cancer
- in-vitro, Bladder, UMUC3
ATP↓, SFN strongly downregulates ATP production by inhibiting glycolysis and mitochondrial oxidative phosphorylation (OXPHOS).
Glycolysis↓,
OXPHOS↓,
HK2↓, SFN weaken the glycolytic flux by suppressing multiple metabolic enzymes, including hexokinase 2 (HK2) and pyruvate dehydrogenase (PDH).
PDH↓,
AKT1↓, SFN decreases the level of AKT1 and p-AKT ser473 , especially in low-invasive UMUC3 cells.
p‑Akt↓,

3194- SFN,    Sulforaphane impedes mitochondrial reprogramming and histone acetylation in polarizing M1 (LPS) macrophages
- in-vitro, Nor, NA
*OXPHOS↑, suggesting that OXPHOS activity is needed for maximal inhibition of M1 marker expression by Sfn
*M1↓,
*IL1β↓, Consistent with our previous study [40], presence of Sfn significantly diminished mRNA expression of il1β, il6, nos2, and tnfα in M1 (LPS) cells
*IL6↓,
*NOS2↓,
*TNF-α↓,
*ROS↓, 0 and 10 μM, impaired M1 marker expression, ROS or NO production and preserved respiratory activity after LPS exposure
*NO↓,
*ACC↑, Sfn prevents the drop of nuclear and cytosolic acetyl-CoA in LPS-stimulated macrophages

2448- SFN,    Sulforaphane and bladder cancer: a potential novel antitumor compound
- Review, Bladder, NA
Apoptosis↑, Recent studies have demonstrated that Sulforaphane not only induces apoptosis and cell cycle arrest in BC cells, but also inhibits the growth, invasion, and metastasis of BC cells
TumCG↓,
TumCI↓,
TumMeta↓,
glucoNG↓, Additionally, it can inhibit BC gluconeogenesis
ChemoSen↑, demonstrate definite effects when combined with chemotherapeutic drugs/carcinogens.
TumCCA↑, SFN can block the cell cycle in G2/M phase, upregulate the expression of Caspase3/7 and PARP cleavage, and downregulate the expression of Survivin, EGFR and HER2/neu
Casp3↑,
Casp7↑,
cl‑PARP↑,
survivin↓,
EGFR↓,
HER2/EBBR2↓,
ATP↓, SFN inhibits the production of ATP by inhibiting glycolysis and mitochondrial oxidative phosphorylation in BC cells in a dose-dependent manner
Glycolysis↓,
mt-OXPHOS↓,
AKT1↓, dysregulation of glucose metabolism by inhibiting the AKT1-HK2 axis
HK2↓,
Hif1a↓, Sulforaphane inhibits glycolysis by down-regulating hypoxia-induced HIF-1α
ROS↑, SFN can upregulate ROS production and Nrf2 activity
NRF2↑,
EMT↓, inhibiting EMT process through Cox-2/MMP-2, 9/ ZEB1 and Snail and miR-200c/ZEB1 pathways
COX2↓,
MMP2↓,
MMP9↓,
Zeb1↓,
Snail↓,
HDAC↓, FN modulates the histone status in BC cells by regulating specific HDAC and HATs,
HATs↓,
MMP↓, SFN upregulates ROS production, induces mitochondrial oxidative damage, mitochondrial membrane potential depolarization, cytochrome c release
Cyt‑c↓,
Shh↓, SFN significantly lowers the expression of key components of the SHH pathway (Shh, Smo, and Gli1) and inhibits tumor sphere formation, thereby suppressing the stemness of cancer cells
Smo↓,
Gli1↓,
BioAv↝, SFN is unstable in aqueous solutions and at high temperatures, sensitive to oxygen, heat and alkaline conditions, with a decrease in quantity of 20% after cooking, 36% after frying, and 88% after boiling
BioAv↝, It has been reported that the ability of individuals to use gut myrosinase to convert glucoraphanin into SFN varies widely
Dose↝, Excitingly, it has been reported that daily oral administration of 200 μM SFN in melanoma patients can achieve plasma levels of 655 ng/mL with good tolerance

1001- SIL,    Silibinin down-regulates PD-L1 expression in nasopharyngeal carcinoma by interfering with tumor cell glycolytic metabolism
- in-vitro, NA, NA
TumCG↓,
Glycolysis↓, Silibinin potently inhibits tumor growth and promotes a shift from aerobic glycolysis toward oxidative phosphorylation.
OXPHOS↑,
LDHA↓,
lactateProd↓,
i-citrate↑,
Hif1a↓,
PD-L1↓, silibinin can alter PD-L1 expression by interfering with HIF-1α/LDH-A

2186- SK,    Shikonin differentially regulates glucose metabolism via PKM2 and HIF1α to overcome apoptosis in a refractory HCC cell line
- in-vitro, HCC, HepG2 - in-vitro, HCC, HCCLM3
Glycolysis↓, shikonin treatment has been reported to inhibit glycolysis by suppressing the activity of pyruvate kinase M2 (PKM2) and to induce apoptosis by increasing reactive oxygen species (ROS) production.
PKM2↓,
Apoptosis↑,
ROS↑,
OXPHOS⇅, Shikonin up-regulated mitochondrial biogenesis to increase mitochondrial oxidative phosphorylation in HepG2 cells, but displayed the opposite trend in HCCLM3 cells.
eff↓, insensitivity of HCCLM3 cells to shikonin treatment.

2413- TTT,    Tumor treating fields (TTFields) impairs aberrant glycolysis in glioblastoma as evaluated by [18F]DASA-23, a non-invasive probe of pyruvate kinase M2 (PKM2) expression
- in-vitro, GBM, U87MG
PKM2↓, Quantitative Western blot analysis and qualitative immunofluorescence for PKM2 confirmed the TTFields-induced reduction in PKM2 expression. TTFields exposure reduced PKM2 expression by 49% at 3 d
Glycolysis↓, Regardless, both outcomes suggest a shift from aberrant glycolysis towards oxidative phosphorylation
OXPHOS↑,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 57

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Catalase↑, 1,   GPx↓, 1,   GSH↓, 3,   H2O2↑, 1,   HO-1↓, 1,   HO-1↑, 2,   Iron↑, 1,   NQO1↑, 1,   NRF2↑, 2,   OXPHOS↓, 22,   OXPHOS↑, 18,   OXPHOS⇅, 1,   OXPHOS↝, 2,   mt-OXPHOS↓, 4,   mt-OXPHOS↑, 2,   ROS↓, 1,   ROS↑, 33,   ROS⇅, 1,   mt-ROS↑, 1,   SOD2↑, 2,  

Metal & Cofactor Biology ⓘ

Ferritin↓, 2,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 13,   ATP↑, 4,   ATP↝, 1,   ATP∅, 2,   compIII↑, 1,   ETC↓, 1,   Insulin↓, 3,   mitResp↓, 2,   mitResp↑, 1,   MMP↓, 7,   MMP↑, 1,   MPT↑, 1,   mtDam↑, 1,   OCR↓, 2,   OCR↑, 5,   PGC-1α↑, 2,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

ACLY↓, 1,   adiP↑, 1,   AKT1↓, 2,   ALDOA↓, 1,   AMPK↑, 4,   Cav1↑, 1,   i-citrate↑, 1,   cMyc↓, 2,   ECAR↓, 4,   ENO2↓, 1,   FASN↓, 1,   FBPase↑, 1,   GAPDH↓, 3,   GDH↓, 1,   glucoNG↓, 1,   glucoNG↑, 1,   glucose↓, 1,   GlucoseCon↓, 3,   GlucoseCon↑, 1,   GLUT2↓, 1,   GlutaM↓, 1,   glyC↓, 1,   Glycolysis↓, 28,   HK2↓, 10,   IDH1↑, 1,   IDH2↓, 1,   lactateProd↓, 8,   LDH↓, 4,   LDHA↓, 4,   LDHB↓, 1,   NADPH↓, 2,   PDH↓, 4,   PDH↑, 2,   PDHA1↓, 1,   PDK1↓, 2,   p‑PDK1↓, 1,   PDKs↓, 2,   PFK↓, 3,   PFK1↓, 1,   PFKP↓, 1,   PGAM1↓, 1,   PGK1↓, 1,   PGM1↓, 1,   PKM2↓, 5,   PPP↓, 1,   SIRT1↑, 1,   SLC25A1↓, 1,   TCA↓, 2,   TCA↑, 1,   Warburg↓, 6,   β-oxidation↓, 1,  

Cell Death ⓘ

Akt↓, 2,   Akt↑, 1,   p‑Akt↓, 1,   Apoptosis↑, 19,   Bak↑, 1,   BAX↑, 2,   Bcl-2↓, 4,   Casp↑, 2,   Casp3↓, 1,   Casp3↑, 9,   cl‑Casp3↑, 1,   Casp7↑, 1,   Cyt‑c↓, 1,   Cyt‑c↑, 6,   Cyt‑c↝, 1,   DR5↑, 1,   JNK↑, 1,   MAPK↓, 1,   Mcl-1↓, 3,   Paraptosis↑, 1,   PUMA↑, 1,   survivin↓, 3,   TumCD↑, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,  

Transcription & Epigenetics ⓘ

HATs↓, 1,   other↓, 1,   other↝, 1,   tumCV↓, 3,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 3,   HSP90↓, 2,  

Autophagy & Lysosomes ⓘ

ATG3↑, 1,   Beclin-1↑, 1,   LAMP2↑, 1,   LC3‑Ⅱ/LC3‑Ⅰ↑, 1,   LC3s↓, 1,   p62↓, 1,   p62↑, 2,   TumAuto↓, 1,   TumAuto↑, 4,  

DNA Damage & Repair ⓘ

DNAdam↑, 5,   P53↑, 3,   P53↝, 1,   PARP↓, 1,   cl‑PARP↑, 2,   cl‑PARP↝, 1,   PCNA↓, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

cycA1/CCNA1↑, 1,   cycD1/CCND1↓, 2,   cycD1/CCND1↑, 1,   cycE/CCNE↑, 1,   TumCCA↓, 1,   TumCCA↑, 7,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 6,   Diff↑, 1,   EMT↓, 4,   p‑ERK↝, 1,   FOXO3↑, 1,   Gli1↓, 1,   HDAC↓, 3,   IGF-1↓, 3,   IGF-1↑, 1,   IGFBP1↑, 1,   mTOR↓, 5,   mTORC1↓, 1,   NOTCH3↓, 1,   PI3K↓, 1,   Shh↓, 1,   Smo↓, 1,   STAT↓, 1,   STAT3↓, 2,   STAT5↓, 1,   TumCG↓, 12,   Wnt↓, 2,  

Migration ⓘ

Ca+2↓, 1,   Ca+2↑, 1,   Ca+2↝, 1,   E-cadherin↑, 1,   Fibronectin↓, 1,   MMP2↓, 1,   MMP9↓, 1,   MMPs↓, 1,   N-cadherin↓, 1,   Snail↓, 1,   Treg lymp↓, 1,   TumCA↑, 1,   TumCI↓, 2,   TumCMig↓, 1,   TumCP↓, 8,   TumMeta↓, 1,   Zeb1↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   EGFR↓, 1,   Hif1a↓, 4,  

Barriers & Transport ⓘ

GLUT1↓, 1,   GLUT3↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   IKKα↓, 1,   IL6↓, 1,   JAK1↓, 1,   M2 MC↓, 1,   NF-kB↓, 2,   PD-L1↓, 1,  

Drug Metabolism & Resistance ⓘ

ABC↓, 1,   BioAv↓, 1,   BioAv↝, 2,   ChemoSen↑, 10,   Dose↑, 1,   Dose↝, 4,   Dose∅, 1,   eff↓, 6,   eff↑, 21,   eff↝, 2,   Half-Life↝, 1,   RadioS↑, 4,   selectivity↑, 14,  

Clinical Biomarkers ⓘ

BG↓, 2,   EGFR↓, 1,   Ferritin↓, 2,   GutMicro↑, 2,   HER2/EBBR2↓, 1,   IL6↓, 1,   LDH↓, 4,   PD-L1↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   AntiTum↑, 1,   ChemoSideEff↓, 3,   neuroP↑, 2,   OS↑, 3,   QoL↑, 2,   QoL∅, 1,   Risk↓, 1,   toxicity↓, 1,   toxicity↝, 4,   TumVol↓, 2,  

Infection & Microbiome ⓘ

CD8+↑, 1,  
Total Targets: 226

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 3,   mt-antiOx↑, 1,   GPx1↑, 2,   GPx4↑, 2,   GSH↑, 1,   OXPHOS↓, 3,   OXPHOS↑, 6,   ROS↓, 6,   ROS↑, 1,   ROS∅, 3,   mt-ROS↓, 1,   SOD↑, 1,   SOD1↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 3,   mitResp↓, 1,   MMP↑, 4,   MMP↝, 1,   OCR↑, 1,   PGC-1α↑, 2,  

Core Metabolism/Glycolysis ⓘ

ACC↑, 1,   AMPK↑, 1,   BMAL1↑, 1,   ECAR↓, 2,   ECAR∅, 1,   FAO↑, 1,   GlucoseCon↑, 2,   Glycolysis↓, 4,   Glycolysis↑, 4,   HK2↑, 2,   LDHB↑, 1,   LDL↓, 1,   NAD↑, 1,   PFKL↑, 2,   PFKM↑, 2,   PFKP↑, 1,   PKM2↑, 2,   PPARα↑, 1,   p‑PPARγ↓, 1,   TCA↑, 1,  

Cell Death ⓘ

Akt↓, 1,   MAPK↓, 1,   YAP/TEAD↑, 1,  

Transcription & Epigenetics ⓘ

Ach↑, 1,   other?, 1,   other↝, 1,   tumCV↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

Diff↑, 1,   mTOR↓, 1,   PI3K↓, 1,   RAS↓, 1,  

Migration ⓘ

CXCL12↑, 1,   TumCMig↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↑, 1,   NO↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,   GLUT1↑, 2,   GLUT4↑, 1,  

Immune & Inflammatory Signaling ⓘ

CRP↓, 1,   IL18↓, 1,   IL1β↓, 2,   IL6↓, 2,   IL8↓, 1,   Inflam↓, 2,   M1↓, 1,   PAR-2↓, 1,   TNF-α↓, 3,  

Cellular Microenvironment ⓘ

pH↑, 1,  

Protein Aggregation ⓘ

Aβ↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 1,   BioAv↝, 1,   Dose↑, 1,   Dose↝, 3,   eff↝, 1,   Half-Life↝, 2,  

Clinical Biomarkers ⓘ

BMD↑, 1,   CRP↓, 1,   IL6↓, 2,   NOS2↓, 1,  

Functional Outcomes ⓘ

AntiAge↑, 1,   cardioP↑, 1,   chemoPv↑, 1,   cognitive↑, 3,   memory↑, 2,   neuroP↑, 1,   toxicity↓, 1,   toxicity∅, 2,  
Total Targets: 87

Scientific Paper Hit Count for: OXPHOS, Oxidative phosphorylation
7 3-bromopyruvate
7 Magnetic Fields
4 salinomycin
3 Ashwagandha(Withaferin A)
3 Dichloroacetate
3 diet FMD Fasting Mimicking Diet
3 Methylene blue
3 Sulforaphane (mainly Broccoli)
2 Citric Acid
2 EGCG (Epigallocatechin Gallate)
2 Honokiol
2 Resveratrol
1 5-Aminolevulinic acid
1 Alpha-Lipoic-Acid
1 Betulinic acid
1 Curcumin
1 Electrical Pulses
1 Chemotherapy
1 diet Short Term Fasting
1 Hydrogen Gas
1 Hyperthermia
1 Magnolol
1 Metformin
1 Proanthocyanidins
1 Phenethyl isothiocyanate
1 Parthenolide
1 Quercetin
1 Rutin
1 Silymarin (Milk Thistle) silibinin
1 Shikonin
1 Tumor Treating Fields
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

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